Loss of Ftsj1 perturbs codon-specific translation efficiency in the brain and is associated with X-linked intellectual disability
Yu Nagayoshi, Takeshi Chujo, S. Hirata, Hiroki Nakatsuka, Chien-Wen Chen, Mayuko Takakura, Kenjyo Miyauchi, Yoshiho Ikeuchi, Becky C. Carlyle, Robert R. Kitchen, Tsutomu Suzuki, Fumiki Katsuoka, Masayuki Yamamoto, Yu‐ichi Goto, Motomasa Tanaka, Kiyohisa Natsume, Angus C. Nairn, Tsutomu Suzuki, Kazuhito Tomizawa, Fan‐Yan Wei
Abstract
in the brain, resulting in a slow decoding at Phe codons. Ribosome profiling showed that translation efficiency is significantly reduced in a subset of genes that need to be efficiently translated to support synaptic organization and functions. Ftsj1 KO mice display immature synaptic morphology and aberrant synaptic plasticity, which are associated with anxiety-like and memory deficits. The data illuminate a fundamental role of tRNA modification in the brain through regulation of translation efficiency and provide mechanistic insights into FTSJ1-related XLID.